This proposal constitutes a broad clinical research program which is designed to gain new insight into conditions of normal and abnormal human thyroid hormone metabolism. For organizational purposes, the program is divided into three general categories: 1) Hypothalamic-pituitary studies, 2) studies of thyroid function, and 3) peripheral thyroid hormone metabolism. Methods for direct measurement of thyrotropin (TSH) and other human thyroid stimulators(HTS), thyroidal iodine (TIR), thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (R-T3) and in vivo conversion of T4 to T3 and R-T3 are utilized in these studies. The in vivo influence of thyroid hormones on adenylate cyclase-cyclic AMP systems (cAMP) generation is also evaluated in these investigations.